The purpose of this proposal is to study the pathogenesis of secondary bacterial infections following influenza infection. This year, the United States has pledged over $334 million dollars in international aid for countries battling influenza. In early 2000, influenza was the 7th leading cause of death in the United States alone, making it a very important public health concern. When addressing the primary cause of mortality, secondary bacterial infections following influenza account for 35- 40% of the mortality observed following viral infection. This is especially germane to the elderly population, where pneumonia alone or as a complication of flu is the leading infectious cause of death. Our objective is to understand the mechanism involved in the pathogenesis of increased susceptibility to secondary bacterial infection and thereby adopt specific therapeutic strategies that impact significant risk reduction in mortality and morbidity from influenza. Research Design and Methods: We will assess the effect of an overactive Th1 response in causing increased susceptibility to secondary bacterial infections, and also study the effects of an over-exuberant Th1 response on various effector cells in the lung. Finally, we will test therapeutic modalities that will target the over-exuberant response to decrease the risk of secondary bacterial infections. To address these objectives we will be using a rodent model for influenza infection, and then study their ability to clear bacteria following viral infection, exposing them to various anesthetics and drugs to modulate the immune response to viral infection. For testing the effect of the viral infection on various effector cells, we will isolate the effector cells from the BAL fluid of the animal and test these cells with various assays developed in the laboratory. [unreadable] [unreadable] [unreadable]